This application claims priority to U.S. Provisional Application No. 61/405,384 filed Oct. 21, 2010, and U.S. Provisional Application No. 61/481,602 filed May 2, 2011, the disclosure of which are both hereby incorporated by reference in their entireties.
Ketorolac or 5-benzoyl-2,3-dihydro-1H-pyrrolizine-1-carboxylic acid, is a known non-steroidal anti-inflammatory agent and has analgesic and anti-inflammatory properties. Ketorolac is described in U.S. Pat. No. 4,089,969.
Ketorolac has considerably higher analgesic and anti-inflammatory activity than many other non-steroid anti-inflammatory drugs. Most significantly, it has higher analgesic activity than morphine, without the well-known side effects of the latter. See, e.g., “Ketorolac—A review of its pharmacodynamic and pharmacokinetic properties and its therapeutic potential”, Drugs 39(1): 86-109, 1990.
The drug is currently administered as the racemic mixture orally or by injection and is commercially available in forms suited for such modes of delivery. Ketorolac tromethamine salt for intramuscular and intravenous administration is available at concentrations ranging from 1.5% (15 mg in 1 ml) to 3% (60 mg in 2 mls). Typically, for multi-dose treatment, the recommended dose is 30 mg of drug every 6 hours. In certain situations, the drug is given as a loading dose of 30 to 60 mg followed by subsequent injections of half the loading dose (15 to 30 mg) every 6 to 8 hours. The total daily dose of the drug as such is in the range of 60-120 mg. The administration of multiple injections is not convenient or well tolerated by patients and bolus administration of the drug either intravenously or intramuscularly can result in a higher incidence of side effects.
Ketorolac is also available as oral tablets and nasal spray. However, these formulations are insufficient to manage moderately severe acute pain that requires analgesia at the opioid level, e.g., in a post operative setting.
Although continuous infusion of ketorolac has been contemplated, the preparation of such formulations in an acute setting has issues with respect to dosing errors, safety issues and maintaining a sterile, stable formulation.
There exists a need in the art for a ready to use ketorolac formulation that is suitable for direct administration to patients for the treatment of analgesia, e.g., in an acute post-operative setting.
All references disclosed herein are hereby incorporated by reference in their entireties for all purposes.